tbuckley/cabot-search huggingface dataset:
Gestational trophoblastic neoplasia: 14-year experience from a single institution.
Authors: Katia Roque Perez, Melanie Wendy Castro-Mollo, Heberth Daniel Vallejos, Rossana Ruiz, Marco Galvez-Nino, Natalia Valdivieso, Ofelia Coanqui, Mivael Olivera Hurtado de Mendoza, Joan Perez, Aldo Lopez, Carlos Velarde, Ramon Andrade De Mello, Luis Mas
Journal: Journal of Clinical Oncology (2022)

e17529 Background: Gestational trophoblastic neoplasia (GTN) is a rare tumor with an excellent prognosis. With the advent of multiagent chemotherapy, cure rate improved to nearly 100% in the low-risk group (LR). However, in developing countries it is lower, especially in the high risk (HR) group. Herein, we describe our experience with management and survival of GTN over a 14y period. Methods: Retrospective study based on case review of women with newly diagnosed GTN between 2005 and 2019 at Instituto Nacional de Enfermedades Neoplasicas (INEN), Lima- Peru. Primary outcome measure was complete remission (CR) by 12 months following completion of therapy and 3y overall survival (OS). Risk score was established according to the International Federation of Gynecology and Obstetrics (FIGO) with patients with scores &lt; 7 and ≥7 being classified as LR and HR, respectively. A subgroup with score ≥13 was defined as ultra-high risk (UHR) group. Results: 172 patients with GTN were included, median age was 30 years (range 18-54 y). Choriocarcinoma was the most frequent histology in 54.6%, however, in 38% it was not determined. The most common metastatic sites were lungs (66%) and brain (15%). Median FIGO risk score was 10 points (range 1- 21). Accordingly, 8% and 82% of patients belong to LR and HR group; 41% of patients with HR had a score ≥13. Regarding treatment, 5 patients (16%) in the LR group were treated with surgery only and 84% received oral methotrexate; while all patients in the HR group received multidrug chemotherapy: 85% received etoposide, methotrexate and dactinomycin (EMA)/ cyclophosphamide and vincristine (CO), 10.6% received etoposide, methotrexate, actinomycin-D (EMA)/ etoposide and cisplatin (EP) and 2% received other regimens. CR was ultimately achieved in 83% of cases overall (100%, 80% and 73% in LR, HR and UHR group, respectively). 16% had persistent disease and relapse occurred in 5% of patients who had previously achieved CR. Early death (within 4 weeks of initiating therapy) occurred in 4.6% (8/31). 3y-OS was 82%, after excluding early deaths, the survival rate was 86%. Conclusions: In our series, HR disease is the most frequent presentation and almost half of this cases correspond to the UHR group. Remission rate in the LR group is similar to that reported in other series, however it is lower in HR and UHR group. Having said this, it represents the data of a high-risk cohort of patients in a resource-constraint setting. This data is being used to identify strategies for improvement of results, especially in ultra-high risk group.
Vaccinations for Patients With Cancer and Cancer Survivors
Authors: Maria Alma Rodriguez
Journal: Journal of the National Comprehensive Cancer Network (2022)

Patients with cancer and cancer survivors are vulnerable to infection, rendering vaccination a necessary intervention. The vaccination process represents a unique challenge in these populations—it is often impossible or impractical to delay the start of cancer treatment for immunizations, and vaccines may fail to trigger an appropriate protective immune response in immunocompromised patients and cancer survivors, with residual immune deficits. Additionally, live attenuated vaccines are contraindicated due to an increased risk of prolonged shedding and disease presence. The current NCCN Guidelines for Survivorship, which reflect the most up-to-date, evidence-based data relating to survivorship, detail the appropriate immunization practices in these highly susceptible populations.
Is a quantitative analysis of dynamic contrast-enhanced MRI of added value for prostate cancer diagnosis?
Authors: S. Turco, C. Dinis Fernandes, R. Miclea, I.G. Schoots, P. Nooijen, H. Van Der Linden, J. Barentsz, S. Heijmink, H. Wijkstrah, M. Mischi
Journal: European Urology (2022)
Extensive 177Lu-PSMA Radioligand Therapy Can Lead to Radiation Nephropathy with a Renal Thrombotic Microangiopathy–like Picture
Authors: Hannah Schäfer, Sarah Mayr, Maike Büttner-Herold, Karina Knorr, Lisa Steinhelfer, Carsten A. Böger, Jürgen E. Gschwend, Uwe Heemann, Matthias Eiber, Christoph Schmaderer, Robert Tauber
Journal: European Urology (2022)
Deep learning algorithm to predict pathologic complete response to neoadjuvant chemotherapy for breast cancer prior to treatment.
Authors: Rachel Choi, Marina Joel, Miles Hui, Sanjay Aneja
Journal: Journal of Clinical Oncology (2022)

600 Background: Pathologic complete response (PCR) to neoadjuvant chemotherapy (NAC) is associated with improved disease-free survival and overall survival in patients with breast cancer. Predicting PCR at the patient level prior to treatment initiation would allow physicians and patients to focus on therapies with the highest likelihood of success and minimize unnecessary toxicities from chemotherapy. We hypothesize that pre-treatment prediction of PCR is possible through a deep neural network algorithm trained on breast MRI imaging obtained prior to treatment. Methods: 126 tumors from patients treated with neoadjuvant chemotherapy for T3 stage breast cancer at a single institution from 2002 to 2006 were analyzed. In total, 3780 MRI slices were included. 3 MRI contrast phases (pre, immediate post, delayed post) from each slice were used as individual inputs to create separate model predictions of PCR. The 2-D CNN was trained over 50 epochs on the training set. The model was tested on the isolated test set (30% of samples). Results: Average model prediction accuracy over the total test set using a single phase of contrast (pre-, immediate post-, or delayed post-) was 90.4%. Concordance adjustment was conducted, with exclusion of slices that had produced discordant predictions across different contrast phase inputs. This resulted in an increase of overall model accuracy to 97.6%. Model accuracy was similar across subsets of age and tumor size despite differences in PCR rates. However, model accuracy was significantly lower in the triple-negative disease group. Conclusions: We demonstrate a deep neural network that accurately predicts PCR based on breast MRI imaging taken prior to NAC initiation. Our findings represent the promise of deep learning algorithms in providing personalized prognostic data for physicians and patients. [Table: see text]
Adjuvant chemotherapy is associated with an overall survival benefit regardless of age in patients with ER+/HER2-breast cancer with 1-3 positive nodes and Oncotype DX recurrence score 20 to 25: A National Cancer Database analysis.
Authors: Lifen Cao, Christopher W. Towe, Xun Luo, Nickolas Stabellini, Amanda L. Amin, Alberto J. Montero
Journal: Journal of Clinical Oncology (2022)

540 Background: Based on the results of the RxPonder trial, post-menopausal women over age 50 with estrogen receptor (ER)+ breast cancer, 1-3+ nodes, and a 21-gene Oncotype DX recurrence score (RS) score of &lt;25, did not benefit from receiving adjuvant chemotherapy. By contrast, adjuvant chemotherapy was beneficial in premenopausal women. We aimed to replicate the RxPonder trial using a larger sample sizes with real world data to determine whether a threshold with RS exists where adjuvant chemoendocrine therapy (CET) is beneficial regardless of age. Methods: The National Cancer Database (NCDB) was queried for women with ER+, human epidermal growth factor receptor 2 (HER2) negative breast cancer, 1-3 positive axillary nodes, and RS &lt;25 who received endocrine therapy (ET) only or CET. Interaction was explored between CET and age as a surrogate for menopausal status in the Cox regression models. Results: The final analytic cohort included 28,427 eligible women: 7,487 (26.3%) received adjuvant CET and 20,940 (73.7%) ET. In the entire cohort, RS had a normal distribution, with a median score of 14. After correcting for demographic and clinical variables, a threshold effect was observed with RS &gt;20 being associated with a significantly inferior overall survival (OS) (P value range: &lt; 0.001-0.019). In women with RS of 20-25, CET was associated with a significant improvement in OS compared to ET alone, regardless of age (age &lt; = 50: HR = 0.334, P = 0.002; age &gt; 50: HR = 0.521, P = 0.019). Conclusions: Among women with ER+/HER2- breast cancer with 1–3 positive nodes, and RS of 20-25, in contrast to the RxPonder trial we observed that CET was associated with an OS benefit in women regardless of age.
HGG-51. Uncovering therapeutic vulnerabilities in mismatch repair-deficient gliomas
Authors: Adam Boynton, Sangita Pal, Ryan Johnston, Naomi Currimjee, Kenin Qian, Mehdi Touat, Nicole Persky, Amy Goodale, James Berstler, Lisa Miller, Alex Guletsky, Keith L Ligon, Rameen Beroukhim, Pratiti Bandopadhayay
Journal: Neuro-Oncology (2022)

Abstract INTRODUCTION: We have observed that approximately 26% of recurrent gliomas acquire hypermutation following treatment with temozolomide (TMZ). Intriguingly, 91% of these tumors harbor mutations in mismatch repair (MMR) genes. Since MMR deficiency confers resistance to TMZ, strategies to target MMR-deficient gliomas stand to impact many patients. METHODS: We ablated the MMR genes MSH2, MSH6, MLH1, and PMS2 using an all-in-one sgRNA-CRISPR/Cas9 expression vector to generate isogenic MMR knockouts in patient-derived glioma cell lines. We characterized the gene expression profiles of these MMR-deficient glioma models and leveraged high-throughput drug screens and genome-scale CRISPR/Cas9 dropout screens to identify therapeutic vulnerabilities induced by loss of MMR. RESULTS: We show that loss of each major MMR gene confers resistance to TMZ. Gene set enrichment analysis of our MMR-deficient knockouts shows enrichment of several hallmark gene sets including DNA repair and G2M checkpoint signatures, and our genome-wide CRISPR dropout screen reveals that MMR-deficient cells are preferentially dependent on a number of genes involved in DNA repair and cell cycle, along with several other pathways. Lastly, the high-throughput drug repurposing (REPO) screen shows that loss of MMR confers differential dependencies to small molecule inhibitors. CONCLUSIONS: Using CRISPR/Cas9 to knock out individual MMR pathway members allows us to systematically study the response of MMR-deficient cells to alkylating agents in an isogenic context. Importantly, these isogenic models reveal that MMR-deficient glioma cells possess novel genetic dependencies and sensitivities to small molecules, which may inform future therapies for MMR-deficient tumors.
Identification of novel N-terminal splice variants in the DCM-associated gene RBM20
Authors: A Gaertner, A Brodehl, K Sielemann, R Knoll, J Gummert, H Milting
Journal: Cardiovascular Research (2022)

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Erich und Hanna Klessmann Foundation Introduction Mutations in human RBM20, encoding the RNA binding protein 20, cause dilated cardiomyopathy (DCM). Within the nucleus RBM20 partially colocalies with other splicing factors. Sequencing of the cardiac transcriptome of a RBM20-deficient rat model revealed RBM20-dependent regulation of myocardial alternative splicing. We identified several carriers of RBM20 mutations. In the literature, it is postulated that in myocardial tissue only one cardiac form of RBM20 with transcription start in exon 2 is expressed. However, it remains unclear why in the heart this alternative start codon is used. Furthermore, the function of putative different transcripts is unknown. Methods We analyzed human myocardial cDNA by 5’RACE to identify novel 5’-terminal RBM20 transcripts using gene specific primers within exon 2. Furthermore, we performed RNA-Seq analysis to detect different RBM20 transcripts directly in the human heart. Results By 5’RACE we could identify additional RBM20 exons localized within the first intron. The usage of two of these exons (internal exons, IE1 and IE2) instead of exon 1 results in transcripts with translation starting in the second exon. The usage of the third alternative internal exon (IE3) might result in a protein differing from full length and cardiac RBM20. Furthermore, we identified transcripts using an alternative exon, which is localized upstream of exon 1. In addition, a transcript comprising exon 1 and 2 of RBM20 was also detected by 5’ RACE. Using RNA-Seq we verified the expression of the transcripts containing exon 1, IE1 and IE2 in the human heart, respectively. Conclusions Here, we present first data on different N-terminal RBM20 transcripts in the human myocardium. In contrast to previous assumptions we identified different splicing forms of RBM20 with unknown functional impact in the human heart. As RBM20 is a DCM-associated gene, the function of the different RBM20 splicing variants might be interesting with respect to cardiomyopathies.
OTHR-34. Identifying mechanisms of microglia-tumor cell interactions in retinoblastoma
Authors: Anike Pohlmann, Teresa Gerling, Carolin Walter, Viktoria Melcher, Flavia W de Faria, Alina Disch, Deniz Kanber, Julia Wöstefeld, Laura Steenpass, Dietmar Lohmann, Tatsiana Ryl, Nicole Riedel, Petra Ketteler, Stefan Schönberger, Saskia Ting, Ivan Bedzhov, Tobias Kiefer, Mael Lever, Sabrina Schlüter, Eva Biewald, Nikolaos Bechrakis, Thomas K Albert, Kornelius Kerl
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: Treatment-related long-term sequelae and chemotherapy resistance diminish the success of retinoblastoma (RB) treatment. To unravel the mechanisms leading to tumor progression and resistance we examined the intratumoral cellular heterogeneity of RB and its interactions with cells of the tumor microenvironment (TME). METHODS: We used single-cell RNA (scRNA-seq) and ATAC sequencing (scATAC-seq) as well as spatial transcriptomics to analyze and compare RB samples from patients with or without previous chemotherapy (chemo-treated vs. naïve). In addition, we developed a 3D model by injection of RB and TME cells into retinal organoids, which mimics the heterogeneous surrounding of the tumor in a spatially and functionally organized manner. RESULTS: ScRNA-seq revealed a high intratumoral heterogeneity of tumor cells representing distinct developmental stages from progenitors to more differentiated photoreceptor cells. The predominant cell type in the TME was M2-activated microglia (MG). M2-MG exerted multiple receptor-ligand interactions with RB tumor cells which were not found in non-diseased retinas. These tumor-specific cellular interactions regulate multiple signaling pathways (e. g. VEGF-, WNT-, BMP-, PGF- signaling) known to be involved in RB progression. By comparing chemo-treated and chemo-naïve RB samples we were able to identify treatment-resistant and -sensitive subpopulations of tumor cells. Finally, data from our RB-retina in vitro model highlighted the impact of RB cells on gene expression programs of normal retinal cells. CONCLUSION: In summary, we deciphered the intratumoral heterogeneity of RB, uncovered an intricate network of microglia-tumor cell interactions that connects numerous important signaling pathways, and further identified chemotherapy-resistant/sensitive tumor cell populations. The latter observation could prove to be very helpful in the development of novel therapeutic approaches in the treatment of RB.
OTHR-11. The effects of the COVID-19 Pandemic on the time to diagnosis in pediatric patients with Primary central nervous system tumors
Authors: Tyler Canova, Neil McNinch, Alexis Judd, Sarah Rush, Erin Wright
Journal: Neuro-Oncology (2022)

Abstract Primary central nervous system (CNS) tumors are a leading cause of death and disability amongst pediatric cancer patients. The early identification of symptom onset is critical in preventing diagnostic delays. In 2018, Akron Children’s Hospital published data on our response time to brain tumor diagnosis and launched educational programs in an effort to decrease diagnostic delays. The goal was to reduce the total diagnostic interval (TDI) in our patient population and reduce tumor- and treatment-related morbidities for these patients. Our post intervention group (2018-2021) was drastically affected by the numerous hospital changes secondary to the COVID-19 pandemic. We sought to examine the impact of COVID-19 related changes on TDI and attempted to identify groups at potential increased risk for diagnostic delays due to the unique pandemic constraints. A retrospective chart review was performed on patients at Akron Children’s Hospital to evaluate both for pre- (diagnosed Jan 1, 2018-February 29, 2020) and post-COVID-19 (diagnosed Mar 1, 2020-June 8, 2021) groups. Both subsets were evaluated statistically and were similar in all respects including demographics, symptomatology, tumor location, tumor type, and survival. The pre-COVID-19 group demonstrated a median TDI of 43.5 days, while the post-COVID-19 group demonstrated a 30-day median. The TDI for low-grade lesions increased from 32 to 59 days and for high-grade lesions decreased from 60 to 27.5 days in the post-pandemic cohort. Overall, this demonstrates a maintained average time to diagnosis for patients despite the pandemic restrictions in place. In addition, the differences in low vs. high-grade lesions suggest that tumors with a more subtle onset of symptoms were disproportionately affected, and highlight a population for intervention during the continued pandemic.
Artisan trial protocol: A single center, open-label, phase II trial of the safety and efficacy of TheraSphere selective internal radiation therapy (SIRT) in the treatment of inoperable metastatic (liver) neuroendocrine neoplasia (NENs).
Authors: Rohini Sharma, Joanne Evans, Caroline Ward, Florian Wernig, Robert Thomas
Journal: Journal of Clinical Oncology (2022)

e16208 Background: Patients(pts) with NENs present with advanced, unresectable disease, with liver metastases. Liver metastases dictates prognosis. SIRT allows targeted high dose radiation directly to tumours, with relative sparing of the surrounding liver tissue. ArTisaN is a phase II study assessing efficacy and tolerability of SIRT using TheraSpheres for management of liver metastases secondary to NENs. Methods: Pts with liver dominant NENs will receive up to 2 TheraSphere treatments. Pts will be followed until disease progression for up to 2-years. Primary endpoints: objective response rate (ORR) within the treated liver volume, incidence of adverse events. Secondary endpoints: progression-free survival (PFS), overall (OS) and quality of life (EORTC QLQ-C30 and QLQ-GI.NET21). Assuming ORR 40%, sample size 24 patients-95% confidence interval will extend 20% in either direction. Results: 13 pts completed therapy: 69% female, primary site: 23% pancreatic, 31% small bowel. Grade: 54%-1, 46% - 2. 69% had previously received more than one line of systemic therapy including 7 who had previously received peptide receptor radiotherapy. 92% received bilobar treatment-average dose 2.49GBq administered. Hepatic ORR-69%. Grade 3 treatment related events occurred in 2 patients–1 ischaemic limb and 1 radiation induced hepatitis. Quality of life-maintained across all parameters. At the time of analysis, 5 pts had progressed, 3 had extrahepatic progression. Median PFS was 15.4 months (95%CI 11.5-19.4) and median OS was 18.5months (95%CI 7.4-29.6). Conclusions: Theraspheres is a safe and effective therapy for the management of patients with liver dominant disease from NENs. Clinical trial information: NCT04362436.
Management of refractory ascites
Authors: Florence Wong
Journal: Clinical and Molecular Hepatology (2022)

The development of refractory ascites in approximately 10% of patients with decompensated cirrhosis heralds the progression to a more advanced stage of cirrhosis. Its pathogenesis is related to significant hemodynamic changes, initiated by portal hypertension, but ultimately leading to renal hypoperfusion and avid sodium retention. Inflammation can also contribute to the pathogenesis of refractory ascites by causing portal microthrombi, perpetuating the portal hypertension. Many complications accompany the development of refractory ascites, but renal dysfunction is most common. Management starts with continuation of sodium restriction, which needs frequent reviews for adherence; and regular large volume paracentesis of 5 L or more with albumin infusions to prevent the development of paracentesisinduced circulatory dysfunction. Albumin infusions independent of paracentesis may have a role in the management of these patients. The insertion of a covered, smaller diameter, transjugular intrahepatic porto-systemic stent shunt (TIPS) in the appropriate patients with reasonable liver reserve can bring about improvement in quality of life and improved survival after ascites clearance. Devices such as an automated low-flow ascites pump may be available in the future for ascites treatment. Patients with refractory ascites should be referred for liver transplant, as their prognosis is poor. In patients with refractory ascites and concomitant chronic kidney disease of more than stage 3b, assessment should be referred for dual liver-kidney transplants. In patients with very advanced cirrhosis not suitable for any definitive treatment for ascites control, palliative care should be involved to improve the quality of life of these patients.